The proposal describes a series of studies with animals and humans to evaluate the metabolic effects of weight loss and regain. These will be done within the Weight Cycling Project, a collaborative project involving investigators from several institutions and disciplines. The primary aim is to determine whether animals and humans adapt to repeated cycles of loss and regain (the "yo-yo syndrome") with increased energy efficiency. Such an effect would make weight loss increasingly difficult with successive cycles because caloric intake would be converted to body weight more efficiently. The first step will be to further develop and refine an animal model of weight cycling and to evaluate metabolic correlates of a cycling effect. Metabolic measures will include lipoprotein lipase activity, adipose tissue morphology, brown fat activity, fat distribution, body composition, metabolic rate, insulin, and thyroid function. Studies will be done using dietary obesity and genetic obesity in animals, and will examine sex differences, pregnancy, the effect of cycling on normal weight animals, and alterations in the nature, frequency, and severity of the loss and regain cycles. Human studies will evaluate weight loss, energy efficiency, and metabolic variables in obese persons who lose and regain on multiple occasions. Studies with wrestlers and football players will be done to evaluate the effects of repeated bouts of loss and regain in highly trained individuals of normal weight. The human and animal studies will provide hypotheses for each other. The active collaboration within a multidisciplinary group of scientists should produce information on the basic processes of body weight regulation. The ultimate aim is to apply the findings to studies on the management and prevention of obesity.